{"doi":"10.3389/fphar.2021.778884","title":"Altered Cortico-Subcortical Network After Adolescent Alcohol Exposure Mediates Behavioral Deficits in Flexible Decision-Making","abstract":"Behavioral flexibility, the ability to modify behavior according to changing conditions, is essential to optimize decision-making. Deficits in behavioral flexibility that persist into adulthood are one consequence of adolescent alcohol exposure, and another is decreased functional connectivity in brain structures involved in decision-making; however, a link between these two outcomes has not been established. We assessed effects of adolescent alcohol and sex on both Pavlovian and instrumental behaviors and resting-state functional connectivity MRI in adult animals to determine associations between behavioral flexibility and resting-state functional connectivity. Alcohol exposure impaired attentional set reversals and decreased functional connectivity among cortical and subcortical regions-of-interest that underlie flexible behavior. Moreover, mediation analyses indicated that adolescent alcohol-induced reductions in functional connectivity within a subnetwork of affected brain regions statistically mediated errors committed during reversal learning. These results provide a novel link between persistent reductions in brain functional connectivity and deficits in behavioral flexibility resulting from adolescent alcohol exposure.","journal":"Frontiers in Pharmacology","year":2021,"id":182417,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9479,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":734730,"name":"Carol A. Dannenhoffer","orcid":"0000-0002-2034-4172","position":1,"is_corresponding":false},{"id":446124,"name":"Amanda Elton","orcid":"0000-0001-9027-1442","position":2,"is_corresponding":false},{"id":355381,"name":"Sung‐Ho Lee","orcid":"0000-0003-2111-5504","position":3,"is_corresponding":false},{"id":318935,"name":"Woomi Ban","orcid":null,"position":4,"is_corresponding":false},{"id":271355,"name":"Yen‐Yu Ian Shih","orcid":"0000-0001-6529-911X","position":5,"is_corresponding":false},{"id":540994,"name":"Charlotte A. Boettiger","orcid":"0000-0003-1853-1574","position":6,"is_corresponding":false},{"id":420248,"name":"Donita L. Robinson","orcid":"0000-0001-7540-3363","position":7,"is_corresponding":false},{"id":420245,"name":"Alexander Gómez‐A","orcid":"0000-0001-8201-9036","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-18T23:48:13.605421Z","pmid":"34912227","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}